Evaluation of Somatic Mutations in Solid Metastatic Pan-Cancer Patients

Authors

Moom Roosan, Chapman UniversityFollow
Isa Mambetsariev, City of HopeFollow
Rebecca Pharaon, City of HopeFollow
Jeremy Fricke, City of HopeFollow
Angel R. Baroz, City of Hope Graduate School of Biological ScienceFollow
Joseph Chao, City of HopeFollow
Chen Chen, City of HopeFollow
Mohd W. Nasser, University of Nebraska Medical CenterFollow
Ramakanth Chirravuri-Venkata, University of Nebraska Medical CenterFollow
Maneesh Jain, University of Nebraska Medical CenterFollow
Lynette Smith, University of Nebraska Medical CenterFollow
Susan E. Yost, City of HopeFollow
Karen L. Reckamp, City of HopeFollow
Raju Pillai, City of HopeFollow
Leonidas Arvanitis, City of HopeFollow
Michelle Afkhami, City of HopeFollow
Edward W. Wang, City of HopeFollow
Vincent Chung, City of HopeFollow
Mihaela Cristea, City of HopeFollow
Marwan Fakih, City of HopeFollow
Marianna Koczywas, City of HopeFollow
Erminia Massarelli, City of HopeFollow
Joanne Mortimer, City of HopeFollow
Yuan Yuan, City of HopeFollow
Surinder K. Batra, University of Nebraska Medical CenterFollow
Sumanta Pal, City of HopeFollow
Ravi Salgia, City of HopeFollow

Document Type

Article

Publication Date

6-3-2021

Abstract

Metastasis continues to be the primary cause of all cancer-related deaths despite the recent advancements in cancer treatments. To evaluate the role of mutations in overall survival (OS) and treatment outcomes, we analyzed 957 metastatic patients with seven major cancer types who had available molecular testing results with a FoundationOne CDx^® panel. The most prevalent genes with somatic mutations were TP53, KRAS, APC, and LRP1B. In this analysis, these genes had mutation frequencies higher than in publicly available datasets. We identified that the somatic mutations were seven mutually exclusive gene pairs and an additional fifty-two co-occurring gene pairs. Mutations in the mutually exclusive gene pair APC and CDKN2A showed an opposite effect on the overall survival. However, patients with CDKN2A mutations showed significantly shorter OS (HR: 1.72, 95% CI: 1.34–2.21, p < 0.001) after adjusting for cancer type, age at diagnosis, and sex. Five-year post metastatic diagnosis survival analysis showed a significant improvement in OS (median survival 28 and 43 months in pre-2015 and post-2015 metastatic diagnosis, respectively, p = 0.00021) based on the year of metastatic diagnosis. Although the use of targeted therapies after metastatic diagnosis prolonged OS, the benefit was not statistically significant. However, longer five-year progression-free survival (PFS) was significantly associated with targeted therapy use (median 10.9 months (CI: 9.7–11.9 months) compared to 9.1 months (CI: 8.1–10.1 months) for non-targeted therapy, respectively, p = 0.0029). Our results provide a clinically relevant overview of the complex molecular landscape and survival mechanisms in metastatic solid cancers.

Comments

This article was originally published in Cancers, volume 13, in 2021. https://doi.org/10.3390/cancers13112776

Recommended Citation

Roosan, M.R.; Mambetsariev, I.; Pharaon, R.; Fricke, J.; Baroz, A.R.; Chao, J.; Chen, C.; Nasser, M.W.; Chirravuri-Venkata, R.; Jain, M.; et al. Evaluation of Somatic Mutations in Solid Metastatic Pan-Cancer Patients. Cancers 2021, 13, 2776. https://doi.org/10.3390/cancers13112776

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The authors

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This work is licensed under a Creative Commons Attribution 4.0 License.